A new indicator mineral methodology based on a generic Bi-Pb-Te-S mineral inclusion signature in detrital gold from porphyry and low/intermediate sulfidation epithermal environments in Yukon Territory, Canada

Porphyry-epithermal and orogenic gold are two of the most important styles of gold-bearing mineralization within orogenic belts. Populations of detrital gold resulting from bulk erosion of such regions may exhibit a compositional continuum wherein Ag, Cu, and Hg in the gold alloy may vary across the full range exhibited by natural gold. This paper describes a new methodology whereby orogenic and porphyry-epithermal gold may be distinguished according to the mineralogy of microscopic inclusions observed within detrital gold particles. A total of 1459 gold grains from hypogene, eluvial, and placer environments around calc-alkaline porphyry deposits in Yukon (Nucleus-Revenue, Casino, Sonora Gulch, and Cyprus-Klaza) have been characterized in terms of their alloy compositions (Au, Ag, Cu, and Hg) and their inclusion mineralogy. Despite differences in the evolution of the different magmatic hydrothermal systems, the gold exhibits a clear Bi-Pb-Te-S mineralogy in the inclusion suite, a signature which is either extremely weak or (most commonly) absent in both Yukon orogenic gold and gold from orogenic settings worldwide. Generic systematic compositional changes in ore mineralogy previously identified across the porphyry-epithermal transition have been identified in the corresponding inclusion suites observed in samples from Yukon. However, the Bi-Te association repeatedly observed in gold from the porphyry mineralization persists into the epithermal environment. Ranges of P-T-X conditions are replicated in the geological environments which define generic styles of mineralization. These parameters influence both gold alloy composition and ore mineralogy, of which inclusion suites are a manifestation. Consequently, we propose that this methodology approach can underpin a widely applicable indicator methodology based on detrital gold

In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies.

BACKGROUND: The rapid and continual viral escape from neutralizing antibodies is well documented in HIV-1 infection. Here we report in vivo emergence of viruses with heightened sensitivity to neutralizing antibodies, sometimes paralleling the development of neutralization escape. METHODOLOGY/PRINCIPAL FINDINGS: Sequential viral envs were amplified from seven HIV-1 infected men monitored from seroconversion up to 5 years after infection. Env-recombinant infectious molecular clones were generated and tested for coreceptor use, macrophage tropism and neutralization sensitivity to homologous and heterologous serum, soluble CD4 and monoclonal antibodies IgG1b12, 2G12 and 17b. We found that HIV-1 evolves sensitivity to contemporaneous neutralizing antibodies during infection. Neutralization sensitive viruses grow out even when potent autologous neutralizing antibodies are present in patient serum. Increased sensitivity to neutralization was associated with susceptibility of the CD4 binding site or epitopes induced after CD4 binding, and mediated by complex envelope determinants including V3 and V4 residues. The development of neutralization sensitive viruses occurred without clinical progression, coreceptor switch or change in tropism for primary macrophages. CONCLUSIONS: We propose that an interplay of selective forces for greater virus replication efficiency without the need to resist neutralizing antibodies in a compartment protected from immune surveillance may explain the temporal course described here for the in vivo emergence of HIV-1 isolates with high sensitivity to neutralizing antibodies

Understanding emotionally relevant situations in primary dental practice. 3. Emerging narratives

Background and aims. Dentists experience considerable occupational stress. Stressful clinical situations can provoke high levels of negative emotions, and situations which are associated with positive emotions tend to be overlooked by practitioners. Reflection regarding difficult situations is encouraged to facilitate learning. Cognitive behavioural therapy (CBT) formulations may be applied to situations appraised both positively and negatively. Analysis and interpretation of the dentist's coping behaviour and the consequent outcomes facilitate learning and reflection upon individual interactions with patients. Method. Twenty primary care dental practitioners in the greater Lincoln area participated in a semi-structured interview which explored their stressful and positive clinical experiences. Some of the episodes were analysed to create CBT formulations. Results and discussion. CBT formulations are presented and the learning points highlighted by this structured presentation are discussed. In particular, it is suggested that this structured reconstruction of events, which highlights dentists' emotions, responses and the transactional effects of coping responses, might well facilitate objective reflective learning either individually or as part of peer to peer support. It should facilitate dentists' emotional processing of events and may thus contribute to stress reduction. Conclusion. CBT formulations of positive and negative dental scenarios may be constructed. It is proposed that this is a useful technique to foster reflection and learning in clinical situations and should lead to improved communication skills and shared decision-making, resulting in fewer complaints and thereby reduced stress. It should also improve dentists' emotional processing

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Base

A study to explore specific stressors and coping strategies in primary dental care practice

Background and Aims: It is widely acknowledged that dentists experience occupational stress. This qualitative study aimed to explore previously identified specific stressors in more detail in order to inform the development of a future stress management programme. Method: Two focus groups of dentists (N: 7 & 6) were conducted to explore, in more detail, nine specific stressors and concepts; being out of one’s comfort zone, zoning out from the patient, celebrating the positive aspects of work, thinking aloud, the effect of hurting patients, the impact of perfectionism, responsibility for patient’s self-care, the emotional impact of difficult situations as a foundation dentist. Participants were also asked for their views on the structure and contents of the proposed stress management package. Verbatim transcripts were subjected to thematic analysis. Results and Discussion: Dentists described the impact of these stressors and their current coping methods; thematic analysis revealed 9 themes which covered the above concepts and a further overall theme of need for control. The findings are elaborated in connection to their relevant stress, coping and emotion psychological theory. Their implications for personal well-being and clinical outcomes are discussed. Conclusion: Dentists’ stressful and coping experiences are complex and it is essential that any stress management programme reflects this and that the skills are easily accessible and sustainable within the context of a busy dental practice

You are Not Welcome: Social Exchanges between Female Spider Monkeys (Ateles geoffroyi)

Group living leads to competition for food between group members. Two types of intragroup food competition may occur: scramble competition, in which all group members use the same resource, such that feeding opportunities are equal for everyone; and contest competition, in which some group members monopolize resources through aggression and dominance. In species in which females disperse from the natal group and immigrate into other groups, immigrant females increase group size and thus possibly food competition. Under these circumstances, other females may use aggression to discourage new females from joining the group. We assessed the distribution of aggression, embraces, and kisses among female spider monkeys (Ateles geoffroyi) in relation to group tenure. We recorded social interactions during 1688 10-min focal animal samples on 11 females in Santa Rosa, Costa Rica. We found that aggression was rare between long-term resident females and aggression rates were not higher during feeding than in other contexts, suggesting there was little contest competition. Long-term residents and less recently immigrant females showed higher aggression rates toward the most recent immigrants than toward other females, especially during the first months after a female immigrated, which coincided with the dry season. We did not find similar patterns for embrace and kiss. These results suggest that other females target aggression toward the most recent immigrants to reduce scramble competition. This finding suggests that group tenure should be included in socioecological models for species with female dispersal. © 2017 Springer Science+Business Media, LL

The estrogen-injected female mouse: new insight into the etiology of PCOS

<p>Abstract</p> <p>Background</p> <p>Female mice and rats injected with estrogen perinatally become anovulatory and develop follicular cysts. The current consensus is that this adverse response to estrogen involves the hypothalamus and occurs because of an estrogen-induced alteration in the GnRH delivery system. Whether or not this is true has yet to be firmly established. The present study examined an alternate possibility in which anovulation and cyst development occurs through an estrogen-induced disruption in the immune system, achieved through the intermediation of the thymus gland.</p> <p>Methods, Results and Conclusion</p> <p>A putative role for the thymus in estrogen-induced anovulation and follicular cyst formation (a model of PCOS) was examined in female mice by removing the gland prior to estrogen injection. Whereas all intact, female mice injected with 20 ug estrogen at 5–7 days of age had ovaries with follicular cysts, no cysts were observed in animals in which thymectomy at 3 days of age preceded estrogen injection. In fact, after restoring immune function by thymocyte replacement, the majority of thymectomized, estrogen-injected mice had ovaries with corpora lutea. Thus, when estrogen is unable to act on the thymus, ovulation occurs and follicular cysts do not develop. This implicates the thymus in the cysts' genesis and discounts the role of the hypothalamus. Subsequent research established that the disease is transferable by lymphocyte infusion. Transfer took place between 100-day-old estrogen-injected and 15-day-old naïve mice only when recipients were thymectomized at 3 days of age. Thus, a prerequisite for cyst formation is the absence of regulatory T cells. Their absence in donor mice was judged to be the result of an estrogen-induced increase in the thymus' vascular permeability, causing de facto circumvention of the final stages of regulatory T cell development. The human thymus has a similar vulnerability to steroid action during the fetal stage. We propose that in utero exposure to excessive levels of steroids such as estrogen has a long-term effect on the ability of the thymus to produce regulatory T cells. In female offspring this can lead to PCOS.</p

An Analysis of News Media Coverage of Complementary and Alternative Medicine

Background: To examine the accuracy and adequacy of lay media news stories about complementary and alternative medicines and therapies. Methodol./Principal Findings: A descriptive anal. of news stories about complementary and alternative medicine (CAM) in the Australian media using a national medical news monitoring website, mediadoctor.org.au. Each story was rated against 10 criteria by two individuals. Consensus scores of 222 news articles reporting therapeutic claims about complementary medicines posted on mediadoctor.org.au between 1 Jan. 2004 and 1 Sept. 2007 were calculated. The overall rating score for 222 CAM articles was 50% (95% CI 47% to 53%). There was a statistically significant (F = 3.68, p = 0.006) difference in cumulative mean scores according to type of therapy: biol. based practices (54%, 95% CI 50% to 58%); manipulative body based practices (46%, 95% CI 39% to 54%), whole medical systems (45%, 95% CI 32% to 58%), mind body medicine (41%, 95% CI 31% to 50%) and energy medicine (33%, 95% CI 11% to 55%). There was a statistically significant difference in cumulative mean scores (F = 3.72, p = 0.0001) according to the clin. outcome of interest with stories about cancer treatments (62%, 95% CI 54% to 70%) scoring highest and stories about treatments for children's behavioral and mental health concerns scoring lowest (31%, 95% CI 19% to 43%). Significant differences were also found in scores between media outlets. Conclusions/Significance: There is substantial variability in news reporting practices about CAM. Overall, although they may be improving, the scores remain generally low. It appears that much of the information the public receives about CAM is inaccurate or incomplete